Methods and compositions containing a berberine compound or berberine related or proto-berberine or derivative compound are provided for the prevention and treatment of metabolic and cardiovascular disorders including metabolic syndrome, hyperlipidemia, obesity, diabetes, insulin resistance, hyperglycemia, hypertension and elevated cholesterol in mammalian subjects. The methods and compositions of the invention are effective for prevention and treatment of metabolic syndrome, hyperlipidemia, obesity, diabetes, insulin resistance, hyperglycemia, hypertension and elevated cholesterol. Additional compositions and methods are provided which employ a berberine compound or berberine related or derivative compound in combination with a second anti-therapeutic agent to yield more effective treatment tools against metabolic disorders, and/or dual activity therapeutic methods and formulations useful to prevent or reduce hyperlipidemia and/or hyperglycemia and one or more causal or related symptoms or conditions associated with hyperlipidemia and/or hyperglycemia in mammalian subjects.